2-Amino-5-iodobenzoic acid can be produced by iodination of 2-aminobenzoic acid, and a method in which 2-aminobenzoic acid is iodinated with iodine in an aqueous solution containing KOH is known (Non-Patent Reference 1). However, in accordance with this method, the yield of 2-amino-5-iodobenzoic acid of the object compound is as small as 72.2%. A half of iodine is recovered as KI without being used for the iodination of 2-aminobenzoic acid, and a step for recovering and recycling iodine is necessary. Therefore, the production process is complicated, and the production cost is great.
A method in which iodine chloride (ICl) is used as the iodinating agent is disclosed (Non-Patent Reference 2). However, crude crystals obtained after the iodination have a brown to purple color, and a step for purification is necessary. Therefore, it is described in Non-Patent Reference 2 that the obtained crude crystals are brought into reaction with a concentrated aqueous solution of ammonia in hot water to form an ammonium salt, the obtained ammonium salt is bleached with sodium hyposulfite, the bleached ammonium salt is then treated with decolorizing charcoal and subjected to acidolysis with hydrochloric acid, and 2-amino-5-iodobenzoic acid of the object compound is obtained with a yield of 76 to 84%. In accordance with this method, the ammonium salt obtained during the purification tends to be colored, and it is necessary that a great care be taken to prevent the coloring. As described above, the yield of 2-amino-5-iodobenzoic acid is small, and many complicated operations are necessary in the method disclosed in Non-Patent Reference 2.
As another route of synthesis of 2-amino-5-iodobenzoic acid, a method in which nitro group in 2-nitro-5-iodobenzoic acid is converted into amino group by reduction is reported (Non-Patent Reference 3). However, in this method, it is difficult that 2-nitro-5-iodobenzoic acid of the raw material is obtained industrially.
In Patent Reference 1, a method in which iodinated biphenyl is produced by bringing biphenyl and iodine or an iodide into reaction with each other in the presence of a solvent, hydrogen peroxide and sulfuric acid is described.
[Non-Patent Reference 1] Carl J. Klemme and James H. Hunter, J. Org. Chem., 5, 227-234, 1940
[Non-Patent Reference 2] V. H. Wallingfold and Paul A. Kruege, Org. Syn., Vol. 2, 349, 1943
[Non-Patent Reference 3] Otto Grothe, J. Prakt. Chem., <2>, 326, 1878
[Patent Reference] Japanese Patent Application Laid-Open No. Showa 63(1988)-91336